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STUDY PROTOCOL Open Access

A complex behavioural change interventionto reduce the risk of diabetes andprediabetes in the pre-conception period inMalaysia: study protocol for a randomisedcontrolled trialJutta K. H. Skau1*, Awatef Binti Amer Nordin2, Julius C. H. Cheah3, Roslinah Ali2, Ramli Zainal4, Tahir Aris5,Zainudin Mohd Ali6, Priya Matzen7, Regien Biesma8,7, Jens Aagaard-Hansen9,1, Mark A. Hanson7

and Shane A. Norris1

Abstract

Background: Over the past two decades, the population of Malaysia has grown rapidly and the prevalence ofdiabetes mellitus in Malaysia has dramatically increased, along with the frequency of obesity, hyperlipidaemia andhypertension. Early-life influences play an important role in the development of non-communicable diseases.Indeed, maternal lifestyle and conditions such as gestational diabetes mellitus or obesity can affect the risk ofdiabetes in the next generation. Lifestyle changes can help to prevent the development of type 2 diabetes mellitus.This is a protocol for an unblinded, community-based, randomised controlled trial in two arms to evaluate theefficacy of a complex behavioural change intervention, combining motivational interviewing provided by acommunity health promoter and access to a habit formation mobile application, among young Malaysian womenand their spouses prior to pregnancy.

Method/design: Eligible subjects will be Malaysian women in the age group 20 to 39 years, who are nulliparous,not diagnosed with diabetes and own a smartphone. With an alpha-value of 0.05, a statistical power of 90 %, 264subjects will need to complete the study. Subjects with their spouses will be randomised to either the interventionor the control arm for an 8-month period. The primary endpoint is change in waist circumference from baseline toend of intervention period and secondary endpoints are changes in anthropometric parameters, biochemicalparameters, change in health literacy level, dietary habits, physical activity and stress level. Primary endpoint and thecontinuous secondary endpoints will be analysed in a linear regression model, whereas secondary endpoints on anordinal scale will be analysed by using the chi-squared test. A multivariate linear model for the primary endpointwill be undertaken to account for potential confounders. This study has been approved by the Medical Researchand Ethics Committee of the Ministry of Health Malaysia (protocol number: NMRR-14-904-21963) on 21 September 2015.(Continued on next page)

* Correspondence: [email protected] Developmental Pathways for Health Research Unit, Department ofPaediatrics, School of Clinical Medicine, Faculty of Health Sciences, Universityof the Witwatersrand, Johannesburg, South AfricaFull list of author information is available at the end of the article

© 2016 Skau et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Skau et al. Trials (2016) 17:215 DOI 10.1186/s13063-016-1345-x

http://crossmark.crossref.org/dialog/?doi=10.1186/s13063-016-1345-x&domain=pdfmailto:[email protected]://creativecommons.org/licenses/by/4.0/http://creativecommons.org/publicdomain/zero/1.0/

(Continued from previous page)

Discussion: This study protocol describes the first community-based randomised controlled trial, to examine the efficacyof a complex intervention in improving the pre-pregnancy health of young Malaysian women and their spouses. Resultsfrom this trial will contribute to improve policy and practices regarding complex behavioural change interventions toprevent diabetes in the pre-conception period in Malaysia and other low- and middle-income country settings.

Trial registration: This trial is registered with ClinicalTrials.gov (www.clinicaltrials.gov) on 30 November 2015, Identifier:NCT02617693.

Keywords: Pre-conception, Pre-pregnancy, Complex behavioural change intervention, E-health, Malaysia, Lifestyleintervention, Motivational counselling

BackgroundDiabetes mellitus (DM) is one of the most commonnon-communicable diseases (NCDs) across the world.Today 387 million people are living with diabeteswhereas 46.3 % remain undiagnosed. The prevalence ofDM is expected to increase to 53 % by 2035 [1]. DM isan important public health concern in Malaysia. Overthe past two decades, the population of Malaysia hasgrown rapidly and the prevalence of DM in Malaysia hasincreased dramatically, along with the prevalence ofobesity, hyperlipidaemia and hypertension. The NationalHealth and Morbidity Survey (NHMS) 2015 estimatedthe prevalence of DM in adults 18 years old and overwas 11.6 % in 2006 and 17.5 % in 2015 [2]. The prevalenceof DM has almost tripled over the past two decades in theyounger generations (20–39 years old) [2, 3].There is a body of evidence showing that lifestyle

changes, such as achieving a healthy body weight, canhelp to prevent the development of type 2 diabetes mellitus(T2DM) [4–6]. Complex behavioural change interventions,or lifestyle intervention trials, have also moved in the pastdecade from targeting high-risk to low-risk populationsand interventions have also been targeted earlier in the lifecourse [7–9]. The use of new communication technologies,such as computer-based interventions, and empowermenttechniques such as goal setting, have been found to behelpful and eventually more effective than other inter-ventions on weight loss and self-management of T2DM[10–13]. Lifestyle interventions seek to delay or halt thedevelopment of T2DM and achieve, e.g. a healthy bodyweight. Goal setting requires a coordinated team effort thatinvolves the person at risk in the decision-making process.Evidence demonstrates that structured, intensive lifestyleprogrammes involving participant education, individualisedcounselling, reduced dietary energy and fat intake, regularphysical activity, and frequent participant contact are ne-cessary to produce long-term weight loss of 5–7 % [14].The Developmental Origins of Health and Disease

(DOHaD) concept describes how during early life (at con-ception, and/or during foetal life, infancy and early child-hood), the environment induces changes in developmentthat have a long-term impact on later health and disease

risk [15]. Early-life influences play an important role in thedevelopment of NCDs, and maternal lifestyle and condi-tions such as gestational diabetes mellitus (GDM) or obes-ity can affect the risk of diabetes in the next generation[16, 17]. Besides complications of pregnancy such asGDM, hypertension, and preeclampsia that directly affectthe pregnancy outcome, the mother’s health during preg-nancy affects her child’s risk of becoming overweight orobese. If the mother makes lifestyle choices that lead tounbalanced nutrition, obesity, stress, smoking and others,her child is more vulnerable to diabetes and other NCDs[18]. Children born to mothers with GDM have a four toeight times higher risk of obesity, glucose intolerance andT2DM in adolescence or young adulthood [19].The Jom Mama project has been designed to develop

an intervention which responds to this rising publichealth challenge, focusing on young Malaysian womenand their spouses. The overall aim of the Jom Mamaproject is to demonstrate whether a complex behaviouralchange intervention will change markers of health in theyoung Malaysian woman in the pre-conception period,before evaluating whether the intervention affects thepregnancy course and the neonate susceptibility to obesityand diabetes. The Jom Mama project is a public-privatepartnership between the Ministry of Health (MoH),Malaysia; the University of Southampton, UK; the Univer-sity of Witwatersrand, South Africa; the Steno DiabetesCentre, Denmark; and Novo Nordisk, Denmark. The pro-ject was initiated in 2012 and is following InterventionMapping guidelines, which is a systematic framework todevelop health promotion programmes [20]. The JomMama project is conducted in three phases; phase 1: todevelop knowledge on the lifestyle of young couples inMalaysia and identify the barriers and facilitators of health[18, 21]; phase 2: to develop intervention matrices and de-velop an intervention package based on the outcome fromphase 1; and phase 3: to implement and evaluate the de-veloped intervention package in a randomised control trial(RCT). In this paper we will present the study protocol foran unblinded, community-based, RCT with two arms toevaluate the complex behavioural change interventiondeveloped in phase 2 of the Jom Mama project.

Skau et al. Trials (2016) 17:215 Page 2 of 12

https://clinicaltrials.gov/ct2/show/NCT02617693

Methods/designAimThe primary objective of the trial is to evaluate the efficacyof a complex behavioural change intervention combiningbehaviour change counselling provided by communityhealth promoters (CHPs) and utilisation of an E-healthplatform to enhance women’s health prior to pregnancy.This will be measured through the change in waist circum-ference after the 8-month intervention period between fe-male subjects exposed to the intervention and femalesubjects exposed to standard of care in a control group.The secondary objectives are to evaluate the efficacy of theintervention on health literacy, dietary habits, physical ac-tivity, sedentary behaviour and stress level.

Study designThe trial is designed as an unblinded, RCT to assess theefficacy of a complex behavioural change interventionaiming to improve the overall health of young womenprior to their first pregnancy. The intervention follow-upperiod is 8 months from randomisation/baseline. After endtrial the subjects will be monitored for a period of12 months for pregnancy. Figure 1 gives the flow diagramof the trial. The trial was designed following the StandardProtocol Items: Recommendations for Interventional Trials(SPIRIT) 2013 statement (see Additional file 1).

Site and participation selectionThe trial will be carried out in the district of Serembanin the state of Negeri Sembilan, Malaysia. This locationwas selected due to Negeri Sembilan having a higherprevalence of diabetes (22.0 %) compared to the nationalprevalence (15.2 %) [22]. Ethnic diversity is one of thekey features of Malaysia and the district of Seremban hasa representation of the three major ethnic groups: Malay,Chinese and Indian, 67.4, 24.6 and 7.3 %, respectively [23].The target subjects will be newly registered married or

engaged women. The woman will be recruited with herspouse, who also will be exposed to the intervention.

Inclusion and exclusion criteriaEligible subjects must meet all the following inclusioncriteria:

1. Female and between the ages of 20–39 years2. Nulliparous3. Not pregnant at the time of signing the informed

consent4. Own a smartphone, with either an Android operating

system version 4.1 and above or iOS operating system7.0 and above, and have Internet access

Subjects meeting any of the following criteria will beexcluded from participation in the trial:

1. Female subject undergoing treatment for type 1 or 2diabetes mellitus

2. Subject not residing in the district of Seremban

ScreeningNewly married or engaged women and their spouses willbe recruited from 2 November 2015, primarily from fivedesignated primary health clinics in the district ofSeremban, whereas Muslim Malay couples are obligated toconduct a pre-marriage screening, which involves a HIV/AIDS test. Other sites in Seremban such as the state mar-riage registration office, temples and churches or other sites(work places, malls, gyms, etc.) will also be approached forrecruitment purposes. A research officer will meet theyoung couples face-to-face and provide an explanation ofthe study rationale and a description of the Jom Mama pro-ject. The women and spouse will be given an opportunityto ask questions and those who are interested in the studywill have their contact details recorded for further contactand arrangements for a baseline visit. If possible, the couplewill be given a clinic appointment for baseline measure-ments at one of the five designated primary health clinics inSeremban. If the couple need time to consider their in-volvement, the research officer will follow-up with threephone calls over the next 3 weeks. If, at these phone callsthe couple accepts participation in the trial, a baseline ap-pointment will be made. If the couple does not answer thethree phone calls or rejects the offer to participate, they willbe dropped from the participation registration list.

InterventionThe intervention has two components. The first compo-nent is an interaction with a CHP who will be in contactwith the women and their spouses during the 8-monthintervention period. These contacts will be a combin-ation of three face-to-face meetings, three phone callsand communication through Whatsapp group chat. TheCHP will use motivational counselling techniques, i.e.motivational interviewing, to support and motivate theyoung women and their spouses to live a healthierlifestyle. The second component is an E-health platformwhich consists of two elements: (1) a mobile applicationin the form of a habit formation application, where sub-jects and spouses can select different challenges forobtaining a healthy diet, more physical activity and lesssedentary behaviour during the intervention period; and(2) a web-based back-end interface which can be accessedby the CHP, which will be her tool to assess the womenand their spouses’ lifestyle situation. The CHP uses adashboard to follow the progress of subject and spouse inperforming the challenges, and uses the information tointeract with the subject and her spouse during the con-tact points in the intervention. Figure 2 presents screenshots of the web-based application the CHPs are using.


The CHP will function as a personal coach to engage, sup-port and guide the young woman and her spouse towardachieving and maintaining a healthier lifestyle. During theinteraction over the intervention period of 8 months, theCHPs will assess the subject and her spouse’s health risksand behaviour, share information on healthy living and

support the subjects and spouses to reach their personalhealth goals. The objectives of each contact point arepresented in Table 1.The CHP role will be carried out by community nurses

who are currently working in primary health care inMalaysia. Prior to the start of the intervention, the

Fig. 1 The flow diagram of the Jom Mama trial


community nurses undertook training in becoming aCHP. This was a 5-day training programme with ses-sions in motivational interviewing techniques, the use of

the E-health platform and basic knowledge of healthydiet and physical activity. The training was carried outby local trainers who are social-psychologists with

Fig. 2 Screen shot from the web application, showing the couples’ dashboard. Screen shot a Shows the overview of all couples under onecommunity health promoter (CHP). The traffic lights give an indication on how active the couple are in performing their selected challenges.The second column indicates when the couple was last active on the mobile application. The last column informs when the CHP has the nextappointment with the couple. Screen shot b Shows the progress over time for one couple. The graphic can shift between wife and husband and,in this example, it is only showing the wife. The upper columns indicate how many times the challenges have been performed per month. The lowercolumns indicate how many times each challenge has been performed


expertise in motivational interviewing techniques, pro-fessional dieticians and physical activity experts. Duringthe trial, refreshment training with the social-psychologisttrainers will take place to support and help the CHPs inaddressing challenging situations they encountered withthe young women and their spouses.The mobile application is a habit-formation applica-

tion, which incorporates personal goal setting, progresstracking and general information on healthy lifestyles.The mobile application has two key components com-prising diet and physical activity. Under each domain

several challenges have been developed which can beselected by the subject on a monthly basis in dialoguewith the CHP. The application will suggest several chal-lenges for healthy eating, such as making healthy foodchoices and healthy food preparation, and interactiveoptions for the subject to stay active and prevent seden-tary behaviour. In addition, the mobile application willalso provide information on what constitutes a healthylifestyle and further information on how to stay healthybefore pregnancy. The mobile application is available oniOS and Android operating systems. Figure 3 presentsseveral screen shots from the mobile application.

Control armSubjects in the control arm will receive standard of care,which is no contact with a CHP and no access to the E-health platform. They will receive one phone call from aresearch officer towards the end of the interventionperiod to remind them of their endpoint visit.

OutcomesPrimary endpointChange in waist circumference was selected as theprimary endpoint because of its validity as a superiormeasurement for assessing abdominal fat content andassociated obesity health risk, as compared to a meas-ure such as body mass index (BMI) [24–26]. Inaddition, there are existing national Malaysian dataon population waist circumference, which allow forthe study results to be comparable on a nationallevel. In the present trial, the primary endpoint ispredicted to provide a 2-cm reduction of waist cir-cumference in the intervention group compared tothe control group, which will reflect a reduction ofcentral fat distribution. The reduction of 2 cm inwaist circumference as a primary endpoint is basedon the mean from a number of studies indicating thata decrement of waist circumference is possible with alifestyle changing intervention over a period of8 months [27–31]. The variation between the twotime-points in these studies was small (standard devi-ation (SD) of 3–5) after the intervention period, andwe therefore assume an expected within-person esti-mate of SD = 5.

Secondary endpointsThe secondary endpoint will be as follows:

1. Change in BMI from baseline to after 8 months2. Change in waist-to-height ratio from baseline to

after 8 months3. Change in waist-to-hip ratio from baseline to after

8 months4. Change in weight from baseline to after 8 months

Table 1 Overview of the objective of each face-to-face andphone call contact point

Contact point Objective

Contact point 1(face-to-face)

Assessment of woman and spouse’s health riskand behaviour: conversation starter

Introduce to use of mobile application

Initiate review of assessments and behaviourchange process

Goal setting


Follow-up on use of mobile application

Provide health information as required

Review and address extrinsic supportiveand inhibiting factors

Introduce proactive coping

Contact point 3(phone)


Follow-up on progress based on initial goalsetting

Provide support and advice


Revise goal setting and set new goals asrelevant



Follow-up on progress based on previouslyset goals



Revise goal setting and set new goals as relevant



Follow-up on progress based on previously set goals



Revise goal setting and set new goals asrelevant


Follow-up on progress based on previously setgoals



Goal setting and planning for the future

End of intervention process


Fig. 3 Screen shots of mobile application. a The main screen, showing the couple’s process for the particular month. The icons on top illustratethe categories of the different challenges selected (two physical activity challenges and one healthy eating challenge). In the middle, is theprogress bar, showing the progress of the user and her spouse for this particular month. Lowest, are the selected challenges listed and how manytimes they should be performed in one week. b By tapping on the challenges, a description of the different challenge is showing (example ofthe healthy eating challenge). c When the challenge has been performed, the subject will ‘check-in’, and by doing that be awarded 2 points forperforming the challenges. d A timer can be set for each challenge, so a reminder will be send to the subject on the given time to perform thechallenge. e The subject is selecting the challenge out of a list set challenges. f The Flash challenge is a bonus challenge, which the subject canselect when it becomes available. This occurs randomly during the intervention period. The Flash challenge will give extra points


5. Change in glycated haemoglobin A1c (HbA1c) frombaseline to after 8 months

6. Change in the fasting lipid profile (total cholesterol,low-density lipoprotein cholesterol, high-densitylipoprotein cholesterol and triglycerides) from base-line to after 8 months

7. Change in blood pressure (systolic and diastolicblood pressure) from baseline to after 8 months

8. Change in the level of health literacy, as measuredby the European Health Literacy SurveyQuestionnaire (HLC-EU-Q47) from baseline to after8 months

9. Change in dietary intake, as measured by a FoodFrequency Questionnaire (FFQ), from baseline toafter 8 months

10.Change in physical activity and sedentary behaviour,as measured by the International Physical ActivityQuestionnaire (IPAQ) used in national healthsurveys in Malaysia, from baseline to after 8 months

11.Change in stress levels, as measured by theDepression Anxiety and Stress Scale 21-items(DASS-21) used by general practitioners in theMalaysian primary health care system from baselineto after 8 months

Other endpointsThe incidence of GDM, confirmed by an oral glucosetolerance test (OGTT), will be assessed in the subjectswho will complete the intervention period and whobecome pregnant in the post-trial monitoring period.The OGTT will be taken at weeks 26–28 of the pregnancy.Data will be captured retrospectively and obtained frommedical charts.

Supportive dataAnthropometric measurements, blood pressure and dataon physical activity, dietary, stress and health literacy willbe collected from the subject’s spouse. Socio-demographicdata and family medical history will be collected fromboth the subject and the spouse. These variables arecollected to adjust for confounding effects.

Sample size calculationThe sample size calculation is based on a 2-cm reduc-tion in waist circumference, in the primary endpoint ofwaist circumference between the intervention and controlarms at 8 months. Assuming a 5 % level of significance(alpha = 0.05), a statistical power of 90 % (beta = 0.10) anda SD of 5 cm using a two-sided t test, 132 women per armare required. Taking into consideration a 20 % drop-outrate, and that 20 % will be pregnant, a total of 660 womenwould be randomised/enrolled to ensure 264 subjects tocover both the intervention and control arms.

RandomisationAt the baseline measurement visit, subjects will berandomised into the intervention and control arms ata 1:1 allocation ratio. Random allocation sequenceswill be computer- generated with block sizes of sixsubjects. Each clinic will be provided with a sufficientnumber of identification (ID) numbers with random-isation codes. When a subject is enrolled in the trial,the study nurse should assign the lowest available IDnumber to the subject from the list of ID numbers.The Institute for Health System Research (IHSR)

under the MoH has prepared the randomisation listand these are distributed to the five designated primaryhealth clinics in Seremban. A copy is maintained by theIHSR.

Data collection, management and analysisStudy conductStudy nurses will be trained to conduct the data collec-tion at the five designated primary health clinics inSeremban district. At the baseline assessment, the prin-ciples of the trial will be explained again for the subjectand spouse and they will be asked to provide consent bysigning the consent form. One original copy of eachform will be kept by the study nurse who will file thedocument on site. One copy of each form will be givento the subjects. The women and their spouses will havelinked ID numbers by assigning each subject and spousethe same ID number with subject ID ending with thenumber ‘2’ and spouse ID ending with the number ‘1’respectively.

Data collectionAt baseline the subjects will undergo measurementsof waist circumference, hip circumference, weight,height and blood pressure by following standardisedprocedures based on World Health Organisation(WHO) STEPS surveillance [32]. Only the subject inthe couple will provide a 10-mL blood sample tomeasure glycated haemoglobin A1c (HbA1c) and afasting lipid profile (triglycerides (TG), low-densitylipoprotein cholesterol (LDL-C), high-density lipopro-tein cholesterol (HDL-C) and total cholesterol (TC)).Due to the need for a fasting lipid profile analysis, thesubject will be asked to come to the clinic after fasting fora minimum of 9 h. In line with this, the data collectiontime-points are planned to be in the morning. The Euro-pean Health Literacy Tool Q-47 (HL-EU-Q47) [33] (HL-EU Consortium 2012), the Malaysian Food FrequencyQuestionnaire (FFQ), modified to be used in the currenttrial [2]; the International Physical Activity Questionnaire(IPAQ) [2]; and the Depression Anxiety Stress Scale 21-items (DASS-21) [34, 35] will be used to collect data onlevel of health literacy, dietary pattern, physical activity


level, and stress level, respectively. Data such as socio-demographic parameters and family history of diabeteswill be collected by structured interviews with the studynurse. The spouse will undergo the same data measure-ments, with the exception of blood sampling. At the endof the data collection, and before subject and spouse leave,data will be checked by the study nurse and site coordin-ator or research officer, to ensure that all data forms andquestionnaires have been filled correctly. When data col-lection is completed the data collection forms and ques-tionnaires will be signed-off by the study nurse and sitecoordinator or research officer. At the end of the baselinevisit, if the subject is randomised to the intervention, thefirst contact with a CHP will be made. The subject andspouse will be introduced to the mobile application and itwill be installed on the subject’s and spouse’s smartphonedevice. If the subject and spouse have sufficient time theCHP will proceed with the first contact point. If the sub-ject and spouse do not have the time, an appointment willbe set in the next 5 days either at the clinic or at the cou-ple’s house. The same measurements, except height,socio-demographic parameters and medical history, de-scribed above will be conducted at the endpoint visit(Table 2).

If a subject becomes pregnant within the 8-monthintervention period, she will be withdrawn from the trial.Exit measurements, which are similar to those at theendpoint visit, will be performed only for subjects whobecome pregnant between 4.1 and 8 months from base-line. For those who become pregnant between baselineand month 4 in the intervention period, no measurementswill be taken.

Data managementAll data will be managed and stored with protection ofdata privacy. Documentation as well as corrections, ifnecessary, will be done in accordance to Good ClinicalPractice guidelines. All protocol-required informationcollected during the trial must be entered on a data col-lection form containing the four questionnaires. The ori-ginal completed data collection form will be send toIHSR, MoH Malaysia, where double data entry will beperformed by two independent data clerks. The com-pleteness, validity and plausibility of data are examined byvalidating programmes, which thereby generate queries.The generated queries will be checked with original datacollection forms and all changes from the original data aredocumented on audit files. Data will be maintained and

Table 2 Data collection at each time-point in the Jom Mama trial

Data collection on woman;● Data collection on spouse; aFFQ Food Frequency Questionnaire, bIPAQ International Physical Activity Questionnaire, cDASS-21Depression Anxiety and Stress Scale 21-items, d Fasting lipid profile: will be measured as a combination of: total cholesterol (TC) level, low-density lipoproteincholesterol (LDL-C) level, high-density lipoprotein cholesterol (HDL-C) level and triglyceride (TG) level; 5Exit point visit will occur if the woman becomespregnant between 4.1 months and 8 months after randomisation


analysed in the statistical Stata programme, version 12.0or higher (StataCorp LP). Monitoring will be performedregularly by an independent clinical research organisationfrom Malaysia to check the completeness of the contentsof records and the data collection forms, the adherence tothe protocol and the progress of enrolment.

Statistical analysisThe null hypothesis is that there is no difference in thechange in waist circumference between the interventionand the control group after the 8-month intervention. Thealternative hypothesis is that the decrement in waist cir-cumference will be bigger in the intervention group com-pared to the control group after the 8-month intervention.A linear regression model will be used to assess the differ-ence in the change of waist circumference from baselineto end of intervention, with the difference in waist circum-ference as the independent variable, treatment (interven-tion versus control) and baseline waist circumference ascovariates. Additional tests will be performed for the im-pact of the intervention in both high- (waist circumfer-ence above 80 cm) and low-risk (waist circumferencebelow 80 cm) groups. This will be done by subgroup ana-lysis or by assessing the proportional changes in the pri-mary endpoint. Each subgroup will also be analysed in alinear regression model. The continuous secondary end-points will be analysed in a linear regression model,whereas the difference in the change of each secondaryendpoint from baseline to end of intervention, will be thedependent variable, treatment (intervention versus con-trol) and baseline value as covariate. Regarding health lit-eracy (HL-EU-Q47), physical activity (IPAQ) and stress(DASS-21) all the variables are ordinal and, therefore, in-dependence between intervention and control groups willbe tested with the chi-squared test. Change in nutrientintakes will be compared between the groups using a gen-eralised linear model, with additional adjustments for totalenergy intake. Nutrient and food patterns before and afterthe intervention will be explored in both groups separatelyby using dimension reduction techniques such as principalcomponent analysis. Multivariate analysis will be per-formed to assess the association between exposure to theintervention, primary endpoints and secondary endpoints(BMI, waist-to-height and waist-to-hip ratio, HbA1c, lipidprofile, blood pressure, health literacy, physical activity,dietary intake and stress level) using linear regressions. Inthis model the secondary endpoint will be included in themodel as covariates and the estimated coefficients will bepresented unadjusted and adjusted for appropriate and/oreffect modifier and/or confounders. Furthermore, interac-tions between the secondary endpoints will also be ex-plored. Several supportive analyses will be performed. Thefirst supportive analysis will explore the relation betweensubjects’ and spouses’ change in waist circumference and

other anthropometric measurements, diet, physical activ-ity, health literacy and stress. A second supportive analysiswill explore whether a short intervention period (subjectswho become pregnant between 4.1 and 8 months in theintervention period), will also have an impact on the pri-mary endpoint and secondary endpoints. A time variableexplaining how long they have been included in the inter-vention will be included in the models as a covariate. Atthe end of the 12-month post-intervention monitoringperiod, a full analysis will be conducted on subjects whobecome pregnant within 12 months after completing theintervention. This will be done by assessing the incidencesof GDM among women who became pregnant betweentreatment groups, using a chi-squared test. Additionally, alogistic regression model to explore associations betweenthe number of subjects with GDM and several secondaryendpoints will be conducted.

Ethical, regulatory and data management considerationsThe study protocol version 4.0 dated 12 August 2015 hasreceived ethical and governance approvals by the MedicalResearch and Ethics Committee of the Ministry of HealthMalaysia (protocol number: NMRR-14-904-21963) on 21September 2015. The study is performed in compliancewith the Declaration of Helsinki. Written informed consentwill be taken from each participant prior to study enrolmentby trained study nurse. The trial was registered at Clinical-Trials.gov, Identifier: NCT02617693 on 30 November 2015.

Safety monitoringIn the event of an abnormal laboratory test results forHb1Ac or a newly suspected or diagnosed health con-cern during a subject’s measurements (i.e. high bloodpressure or a high score in the DASS-21 tool) at baseline/exit point/endpoint, the subject will be referred to theirprimary health care physician for further examination.

DiscussionThis study protocol describes the first community-basedRCT to examine the efficacy of a complex behaviouralchange lifestyle intervention in improving the pre-pregnancy health of young Malaysian couples. Otherstudies assessing the prevention of GDM and T2DMhave mainly focused on high-risk groups or the interven-tion entry point has been in the first trimester of thewomen’s pregnancy [36–40], whereas few RCT studiesexist on low-risk populations or on an intervention entrypoint in the pre-conception period [41]. To developpopulation strategies, instead of targeting high-risk groupsit is imperative to widen the focus to the general popula-tion, especially in a country such as Malaysia where theprevalence of diabetes and obesity has increased alarminglyin the last 10 years [2]. One European study has shownthat limited guidelines and policies exist in this area, as


guidelines and policies are designed to mainly targethigh-risk groups [42]. Therefore, this study may con-tribute evidence to this important area which isneeded to support policy-makers in making rationaldecisions to improve population health.A pilot test was conducted prior to trial implementa-

tion and has identified a number of challenges. A majorchallenge that has been found is that the interventionaddresses a challenging period for young Malaysian cou-ples, whereby busy work schedules and lack of timeaffect participation rates and generate low interest insuch an intervention. While it would be ideal to collectspousal data at baseline and endpoint, it will be madeoptional for the spouse to attend both baseline and end-point visits if they are unable to attend in order to con-tinue with recruitment. Based on these observations, itis expected that the recruitment period will be longerthan initially anticipated.The combination of motivational interviewing

through a CHP and E-health platform is a novel ap-proach. Training the community nurses to become CHPsinvolves an interactive approach beyond their conven-tional training programmes; this provided new learningexperiences for these nurses to build higher capacity inpatient engagement. The E-health platform is also a newexperience for the primary health care services in theSeremban district and considerable time was needed totrain community nurses with the necessary IT skills. An-other key challenge faced was the limited usage of the E-health mobile application due to poor Internet connectiv-ity in the district of Seremban. In mitigating this challenge,Wi-Fi hotspots in the designated primary health clinicshave been set up to enable participating women and theirspouses to download the mobile application in a securedInternet environment. Additionally, several changes havebeen made to the E-health platform to make it morerobust.The proposed trial will not directly assess the long-term

effects of the intervention on the risk of the offspring de-veloping T2DM. Given the complexity of developing,implementing and evaluating complex behavioural changelifestyle interventions, this trial will focus on improvingthe pre-conception health in young women prior to theirfirst pregnancy.

Trial statusThe trial started recruitment in November 2015. Thetrial is expected to be completed by July 2017.

Additional file

Additional file 1: The SPIRIT recommendations for clinical trials protocols.(DOC 117 kb)

AbbreviationsBMI: body mass index; CHP: community health promoter; DASS-21: Depression Anxiety and Stress Scale 21-items; DBP: diastolic bloodpressure; DM: diabetes mellitus; DOHaD: The Development Origins of Healthand Disease; FFQ: Food Frequency Questionnaire; GDM: gestational diabetesmellitus; HbA1c: glycated haemoglobin A1c; HDL-C: high-density lipoproteincholesterol; HLC-EU-Q47: The European Health literacy Survey Questionnaire;ID: identification; IHSR: Institute for Health System Research;IPAQ: International Physical Activity Questionnaire; LDL-C: low-densitylipoprotein cholesterol; MoH: Ministry of Health; NCDs: non-communicablediseases; NHMS: National Health and Morbidity Survey; OGTT: oral glucosetolerance test; RCT: randomised controlled trial; SBP: systolic blood pressure;SD: standard deviation; T2DM: type 2 diabetes mellitus; TC: total cholesterol;TG: triglycerides; WHO: World Health Organisation.

Competing interestsThe study forms part of the Jom Mama project in Malaysia. The Jom Mamaproject is a public-private partnership with the Ministry of Health Malaysia,Novo Nordisk (Denmark), the University of Southampton (UK), the Universityof Witwatersrand (South Africa), and the Steno Diabetes Center (Denmark) toaddress diabetes prevention in Malaysia. The development of the interventionpackage, project management and the costs of the CRO have been funded byan unrestricted grant from Novo Nordisk. The Ministry of Health Malaysia isproviding the funding for human resources and trial implementation. JKHS,JCHC and PM are employed by Novo Nordisk. The Steno Diabetes Center is anot-for-profit institution owned by Novo Nordisk. MAH is supported by theBritish Heart Foundation.

Authors’ contributionsAll authors have collectively contributed to the development of the studyprotocol. ZMA and RA are responsible for the overall trial coordination andimplementation and drafting the first report. JKHS is responsible in assisting thetrial design, overall coordination of the trial, data management and drafting thefirst report and been responsible for the intervention package development.ABAN has been responsible for the intervention package development, assistedin pilot testing and contributed to the implementation of the trial. JCHC isresponsible in assisting the trial design, overall coordination of trialimplementation and assisting with drafting the first report. RZ, TA, RB, JAH,MAH, PM and SAN are responsible for the trial design and the development ofthe intervention package and will be assisting in drafting the first report. Allauthors read and approved the final manuscript.

AcknowledgementsThe authors would like to thank the Director General of Health, Malaysia, forhis permission to publish this article. We greatly acknowledge all the youngcouples who have agreed to participate in the pilot study and the staff ofSeremban Health Office who cooperated with us in conducting the study.The Ministry of Health Malaysia is providing the funding for human resourcesand trial implementation. The development of the intervention package,project management and the costs of the CRO have been funded by anunrestricted grant from Novo Nordisk.

Author details1MRC Developmental Pathways for Health Research Unit, Department ofPaediatrics, School of Clinical Medicine, Faculty of Health Sciences, Universityof the Witwatersrand, Johannesburg, South Africa. 2Institute of Health SystemResearch, Ministry of Health, Selangor, Malaysia. 3School of Medicine andHealth Sciences, Monash University Malaysia, Jalan Lagoon Selatan, 46150Bandar Sunway, Selangor, Malaysia. 4Pharmaceutical Policy and StrategicPlanning Division, Pharmaceutical Services Division, Ministry of HealthMalaysia, Selangor, Malaysia. 5Institute of Public Health, Ministry of Health,Kuala Lumpur, Malaysia. 6State Health Department Negeri Sembilan, Ministryof Health, Seremban, Malaysia. 7Institute of Developmental Sciences, Facultyof Medicine, University of Southampton, Tremona Road, Southampton SO166YD, UK. 8Department of Epidemiology and Public Health Medicine, RoyalCollege of Surgeons in Ireland, Dublin, Ireland. 9Health Promotion Research,Steno Diabetes Center, Gentofte, Denmark.

Received: 11 December 2015 Accepted: 15 April 2016


dx.doi.org/10.1186/s13063-016-1345-x

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http://www.idf.org/diabetesatlashttp://dx.doi.org/10.1002/14651858.CD007675.pub2http://dx.doi.org/10.1371/journal.pone.0039503http://dx.doi.org/10.1002/14651858.CD008776.pub2https://dohadsoc.org/https://dohadsoc.org/http://dx.doi.org/10.1186/1471-2458-14-S2-S6https://www.statistics.gov.my/http://dx.doi.org/10.1002/14651858.CD003054.pub3http://www.who.int/chp/steps/manual/en/http://www.health-literacy.euhttp://dx.doi.org/10.2337/dc15-0511http://dx.doi.org/10.1002/14651858.CD007536.pub2http://dx.doi.org/10.1002/14651858.CD007536.pub2http://dx.doi.org/10.3109/13625187.2014.990088

AbstractBackgroundMethod/designDiscussionTrial registration

BackgroundMethods/designAimStudy designSite and participation selectionInclusion and exclusion criteriaScreeningInterventionControl armOutcomesPrimary endpointSecondary endpointsOther endpointsSupportive dataSample size calculationRandomisation

Data collection, management and analysisStudy conductData collectionData managementStatistical analysisEthical, regulatory and data management considerationsSafety monitoring

DiscussionTrial statusAdditional fileAbbreviationsCompeting interestsAuthors’ contributionsAcknowledgementsAuthor detailsReferences

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